A study of conjunctival impression cytology in patients undergoing allogeneic hematopoietic stem cell transplantation and its relationship with Ocular Graft versus Host Disease

TL;DR

This study examines dry eye symptoms and conjunctival changes in patients after stem cell transplants, finding that ocular graft versus host disease is a major cause of eye problems.

Contribution

The study demonstrates that conjunctival impression cytology is a valuable non-invasive diagnostic tool for early detection of ocular graft versus host disease.

Findings

Ocular graft versus host disease (oGVHD) was diagnosed in 66.67% of eyes with significant dry eye symptoms.

Conjunctival impression cytology showed abnormal cell morphology, including reduced goblet cell density and inflammatory cells, in oGVHD patients.

Goblet cell density correlated with the time since hematopoietic stem cell transplantation, decreasing significantly over time.

Abstract

To assess the proportion of patients with dry eye syndrome and to examine the changes in conjunctival impression cytology (CIC) in all patients undergoing hematopoietic stem cell transplantation (HSCT) by employing CIC as a diagnostic tool for ocular graft vs. host disease (oGVHD).

Every patient who received HSCT underwent a thorough ophthalmic examination, which included visual acuity, an assessment of dry eyes using objective tests such as Schirmer’s I test, tear film break-up time, and subjective tests such as the Ocular Surface Disease Index (OSDI) questionnaire. Conjunctival impression cytology was conducted after that, following informed consent.

This study included 24 eyes from 12 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT), with a mean age of 31.4 ± 11.06 years. Dry eye disease was observed in 28.8% of the cases. Based on the symptoms, 16 eyes (66.67%) were diagnosed with oGVHD. The Ocular Surface Disease Index (OSDI) indicated mild symptoms in 4 eyes (16.67%), moderate symptoms in 11 eyes (45.33%), and severe symptoms in 1 eye (4.17%) in individuals with ocular GVHD. In contrast, 93.55% of eyes without oGVHD exhibited mild symptoms, while 6.71% showed moderate symptoms (p = 0.002).

Objective assessments indicated that Schirmer’s I score was ≤ 5 mm in 50% of the eyes (n = 12), and tear film breakup time was less than 5 seconds (3.85 ± 2.18 seconds) in 29.17% of eyes with oGVHD (p = 0.05). The conjunctival impression cytology (CIC) was abnormal in 9 eyes (37.5%, p = 0.05), revealing changes in cell morphology, such as decreased goblet cell density, reduced cytoplasmic mucin, and inflammatory cells. The average goblet cell density was measured at 190.63 ± 81.00 cells/mm2 in 6 eyes (p = 0.05), showing a correlation with the time since HSCT; specifically, when the interval from HSCT to CIC assessment was 40.67 ± 5.01 months, the goblet cell density significantly decreased to 181.00 ± 76.62 (p = 0.04).

Changes in morphology were observed in 8 eyes with oGVHD (91.7%) compared to 2 eyes without oGVHD (16.67%), with abnormal CIC results in 66.67% of cases (p = 0.02).

This study highlights the significant prevalence of dry eye disease (DED) and ocular surface alterations in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in those diagnosed with ocular graft-versus-host disease (oGVHD). The findings align with previous research, indicating that oGVHD is a leading cause of post-HSCT ocular morbidity, with symptoms ranging from mild irritation to severe ocular surface damage. The significantly higher Ocular Surface Disease Index (OSDI) scores, reduced Schirmer’s I test values, and shorter tear film breakup times (TBUT) in oGVHD patients corroborate established diagnostic criteria for severe tear dysfunction. Moreover, conjunctival impression cytology (CIC) revealed marked goblet cell loss and squamous metaplasia, consistent with prior studies linking these changes to chronic inflammation and epithelial instability in oGVHD. The correlation between longer post-HSCT duration and further reduction in goblet cell density underscores the progressive nature of ocular surface damage in these patients. Given its non-invasive nature and diagnostic accuracy, CIC is a valuable tool for early oGVHD detection, facilitating timely therapeutic intervention and potentially mitigating long-term ocular complications.

Significant alterations in the ocular surface were noted in those who had chronic oGVHD and had undergone allo-HSCT. The Ocular Surface Disease Index (OSDI) score, corneal involvement severity, and Schirmer I test results are key indicators of ocular involvement following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The most notable abnormalities observed in the conjunctival impression cytology of eyes with oGVHD include squamous cell metaplasia and reduced goblet cell density, with lesser changes noted in eyes without oGVHD. Therefore, conjunctival impression cytology is advisable for patients who have received allogeneic HSCT to facilitate the early diagnosis of oGVHD.

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